Polynuclear cyclic oxyketones and derivatives thereof and process of making same



Patented Jan. 19, 1943 UNITED STATES PATENT OFFICE POLYNUCLEAR CYCLIC OXYKETONES AND DERIVATIVES THEREOF AND PROCESS OF MAKING SAME Leopold Ruzicka, Zurich, and Albert Wettstein,

Basel, Switzerland,

rs, by name ments, to Ciba Pharmaceutical Products, In-

corporated, Summit, N. 3.,

New Jersey a corporation of No Drawing. Original application June 15, 1936,

zerland June 18, 1935 20 Claims.

The present application is a division of applicants prior application Ser. No. 85,437, filed June 15, 1936.

Isomeric oxyketones of the saturated or unsaturated androstane-series, whose hydroxyl and drostane-diols-(Szl'l), oxidizing the free carbinol-group (in 3-position) thus produced (if necessary with temporary protection of the double bonds present) to a keto-group and, if desired, purifying and saponifying the keto-ester thus obtained.

A particularly advantageous procedure consists in starting from a mixed di-ester of a diol of the type of the saturated or unsaturated androstanediols, particularly those esters in which the hydroxyl group in 3-position is esterified with an acid radical which is comparatively easily saponifiable, whilst that in 17-position is esterifled by an acid radical which is saponifiable with comparative diificulty. One can also start from a free diol, partially esterify this and oxidise the resulting diol, mono-esterifled in 17-position, in the manner described above, advantageously after purification.

The same oxyketone can be produced by subjecting the free diol, if desired with temporary protection of double bonds present, directly to a partial oxidation and separating from the reaction product the compound which has undergone oxidation at the 3-position.

Finally, it is also possible to obtain those new oxyketones by subjected to a partial reduction a diketone of the type of the androstane-dione- (3:17) and separating from the reduction product the 3-keto-17-oxy-compound.

The carbinol-group in 3-position can also be oxidized to a keto-group by the action of a dehydrogenating agent.

The various methods may be illustrated by the following formulae, in which A01 and Ac: mean the same or different acyl radicals and R repre- Serial No. 85,437. Divided and this application August 16, 1937, Serial No.

159,433. In Switsents hydrogen or a monovalent hydrocarbon radical:

C CH:

H: R C H: C Ha I II partial saponificetlon partial esteriflcation ACr-O CH3 CH3 If C /\/Y dehydrok/ oxidation or genation 0 III CH; OH;

VF? WW VII partial oxidation or dehydrogenation CH3 OH; R

As suitable oxidizing agents for converting III into IV or for converting V into VII there may be used, for example, a hexavalent chromium compound such as chromic acid in glacial acetic acid; furthermore copper oxide and the like. In the oxidation of an unsaturated diol or its ester to an oxyketone or its ester the carbon double linkage is advantageously protected from the action of the oxidizing agent, for example by the attachment of halogen of hydrogen halide; after oxidation the halogen is then again removed, for example by treatment with zinc in glacial acetic acid or benzene, with catalytically activated hydrogen or with an alkali iodide, or the hydrogen halide is again removed by treatment with an alkaline agent such as a tertiary base. The conversion of the free diols into 3-keto-l'7-oxy-compounds by oxidation of the 3-carbinol-group proceeds in a particularly advantageous manner in cases in which the nuclear carbon atom in 17- position is linked to a hydrocarbon radical. When a mixed di-ester is to be subjected to partial saponification there are advantageously used those which contain in 3-position the radical of a lower fatty acid such as acetic acid or formic acid, and in l'i-position the radical of a higher fatty acid such as a valeric acid, or a carbamic acid, benzoic acid, a toluic acid, hexahydrobenzoic acid, or a hydrohalogen acid.

The aforesaid mixed di-esters are obtained by causing to act on a 3-mono-ester of a diol of the type of the saturated or unsaturated androstane diols an acylating agent containing'an acid radical different from that already present in the molecule of the mono-ester.

The partial saponiflcation may be conducted, for example, in methyl alcohol, ethyl alcohol, in a higher alcohol, in dioxane, acetone or the like. If an alcohol is used re-esteriiication generally occurs in addition to the actual saponiilcation,

so that the quantity of alkali solution consumed is frequently considerably less than the calculated quantity. One is therefore not restricted to the use of the calculated quantity of alkali, but may use a larger or a smaller quantity. By this means, as well as by the concentration of the alkali solution and the temperature, the duration of the reaction may be favorably influenced.

Suitable acylating agents for converting II into III and for converting VII into IV are, for instance, acids, acid halides and acid anhydrldes. for example benzoic acid, acetic acid, formic acid, benzoyl chloride, acetyl chloride, acetic anhydride and 'the like, if required in the presence of an acid binding agent such as a tertiary base or an alkali. Particularly when an acid halide or an acid anhydride is used there is advantageously taken for the partial esteriflcation of II only a quantity of acylating agent suflicient for esterifying one hydroxyl-group.

In the partial reduction of VI the hydrogenation is interrupted when there has been absorbed a quantity of hydrogen suflicing for the reduction of one carbonyl-group.

For the dehydrogenation of the carbinol-group to the keto-group there may be used with advantage any of the usual dehydrogenating agents,

for instance selenium, sulfur, or a metallic catalyst belonging to the group of hydrogenating or dehydrogenating catalysts such as copper, platinum, palladium, gold, nickel and the like, if desired in the presence of a hydrogen acceptor such as naphthalene, phenol, cynnamlc acid. fumaric acid or the like.

It is easily possible to isolate in a pure form the oxyketone produced either by direct crystallization or by preparing a suitable derivative. Such derivatives are obtained, for example, by reaction with the usual ketone reagents such as semi-carbazide, thiosemicarbazide, hydroxylamine, aminoguanidine, phenylhydrazine and its substitution products, neutral or basic acylhydrazides. For purification and separation acylation is often useful, for example by means of acetic anhydride, benzoyl chloride, dinitro-benzoyl chloride or the like. By the action of hydrolytically acting agents the above compounds can be split into their components. For separating the 3-keto-compound from any 3-oxy-compound which may have'been formed as a byproduct there have been proved advantageous also the saponines such as digitonine especially when the steric arrangement of the hydroxylhydrocarbon radical such as an alkyl-, aralkylor aryl-group; so also the scope of the 3:17- androstane-diones extends also to the isomeric 3: lfl-aetiocholanediones. The following diols, for

example, are suitable parent materials for the invention: the androstane-diols-(iizl'l), the A or A -androstene-diols- 3 17) the l7-methylor l'i-ethyl-androstane-diols-(3:17), the 17- methylor 17-ethyl-androstene-diols-(3:17), in which in each case the carbinol-groups in both 3- and l'l-positions may be in cis-, or epi-, or in trans-position. Suitable parent materials of the dione-series are among others the androstane-dione- (3 :17), the A -androstene-dione- (3:17) and the aetiocholane-dione-(3:17)."

The new oxy-ketones as well as their esters havepowerful effects on the combs of capons and also on the seminal vesicle.

The following examples illustrate the invention:

Emmple 1 3.76 grams of andostane-diol-(3,l7)-diacetate of the formula CH: CH

of melting point 127:-128 C. are allowed to stand for 48 hours at room temperature in 1000 cc. of n/IOO-methyl-alcoholic potash solution. After concentrating the solution, the l'l-acetoxy-androstane-ol-(3), produced by the partial saponification, is precipitated by addition of water, filtered, washed with water and dried in a vacuum over phosphorus pentoxide. It may be used without further purification for making androstane-ol-(17)-one-(3). For this purpose the product is dissolved in 50 cc. of glacial acetic acid and there is added, while cooling, a solution of 0.8 gram of chromium trioxide in 25 cc. of acetic acid of per cent. strength. After standing for 14 hours at room temperature some methanol is added for the purpose of reducing the small CH1 CH H By recrystallization from hexane or dilute alcohol the latter may be purified. It forms colorless crystals of melting point 182 C.

Instead of the acetate there may also be used the propionate or the butyrate.

Example 2 3.74 grams of A -androstene-diol-(S:17)-diacetate of the formula tion, is precipitated by addition of water, ex-

tracted with ether and obtained by evaporation of the ether. The crude mono-ester thus obtained is purified by recrystallization from hexane, with removal of sparingly soluble constituents and the purified ester of melting point 146-148" C. is taken up in 50 cc. of glacial acetic acid and, while cooling, there is added, drop by drop, a solution of bromine in glacial acetic acid as long as there is immediate decolorization. Finally, also in the cold, there is added 1 gram of chromium trioxide dissolved in 30 cc. of acetic acid of 90 per cent. strength and the whole is allowed to stand overnight at room temperature. The whole is then poured into 1 liter of water, the precipitated product is filtered and washed with much water. The brominated ketone thus obtained is dissolved for the purpose of debrominating it in 50 cc. of glacial acetic acid, and after addition of 20 grams of zinc dust the whole is heated while vigorously shaking for 12 minutes on the boiling water-bath. There follow filtration through a glass filter, washing with a little hot glacial acetic acid, precipitating the solution with water and extraction with ether. The ethereal solution is washed with dilute sodium carbonate solution and water and then evaporated to yield a residue, from which A -androstene-ol-(1'7) -one- (iii-acetate may be isolated by means of its semicarbazone, and after recrystallization from hexane melts at 141 C. By saponiiication it may be converted into the free oxyketone, namely A -andrc|stene-ol-(l7)-one-(3) of the formula which melts at 155 C. When using other esters, there are obtained the corresponding keto-esters in an analogous manner, for instance A -androstene-ol-(l'?)-one-(3)-benzoate of melting point 194-195 C.

1 The propionate of melting point 121-123 The n-butyrate of melting point 111-113 The iso-butyrate of melting point 131-133 The n-valerianate of melting point 109-111 The n-caprinate of melting point 55- 5'? The palmitate of melting point 72- '74 The stearate of melting point 79- 80 which esters may be saponified, if desired.

The double linkage may be protected by chlorine, for example, instead of bromine.

Example 3 1.87 grams of A -3-trans-1'7-cis-androstenedioldiacetate of the formula of melting point 168 C. are dissolved in 370 cc. of methanol and the solution is mixed with a solution of 0.28 gram of potassium hydroxide in a small quantity of methanol. The whole is allowed to stand at 15 C. for 36 hours, whereupon it is exactly neutralized with dilute hydrochloric acid, and the solution is concentrated in a vacuum to 50 ce. It is then diluted with water and the reaction product is taken up in ether and the ethereal solution is dried and evaporated. By fractionally crystallizing the residue from hexane, the l'l-mono-acetate of A -3--trans-1'7-cisandrostene-diol is obtained. This is dissolved in 30 cc. of glacial acetic acid and treated with the calculated quantity (1 mol) of bromine in glacial acetic acid. The bromine is immediately decolorized. There is then added a solution of 1 mol of chromic acid in acetic acid of per cent. strength and the whole is allowed to stand overnight at room temperature. The reaction product is then precipitated by addition of water, filtered, debrominated by shaking in an alcoholic solution for 48 hours with zinc dust and finally purified byrecrystallization from hexane. From the acetate of A -androstene-cis-ol-(I'D-one- (3) of melting point C. there is obtained by saponification with methyl alcoholic potash of 2 per cent. strength the A= -androstene-cis-ol- 117) -one-(3) 01' the formula CH: CH:

A51 -3-trans-1'l-cis-androstene-diol diacetate is obtained by acetylation of A -3-trans-1'l-vlsandrostene-diol-3-acetate, which is itself formed together with 3-trans-1'i-trans-diol-3-acetate by hydrogenation of N -trans-dehyi'lroandrosterone-acetate.

Example 4 2.31 grams of A =-3-trans-17-trans-androstene-diol-3-acetate-17-benzoate of the formula CHu.C0.0

of melting point 178-180" C. are mixed with 500 cc. of methyl alcohol. The mixture is stirred for a long time (about 50 hours) at room temperature and there is added, gradually by drops, a methyl alcoholic solution of 0.3 gram of potassium hydroxide. After neutralization the whole is highly concentrated in a vacuum: the crude product is precipitated by the addition of water, extracted by means of ether and the ethereal solution is evaporated. The residue is crystallized from hexane, yielding brilliant needles of melting point 222-223 C. of the A -3-trans-17- trans-androstene-diol-l7-benzoate.

This mono-ester is dissolved in 50 cc. of glacial acetic acid and there is added, while cooling and in drops, the calculated proportion of a solution of bromine in glacial acetic acid. Finally, 0.5 gram of chromium trioxlde dissolved in 15 cc. of acetic acid of 90 per cent. strength is added in the cold and the whole is allowed to stand over-night at room temperature, during which time the oxidation product in part crystallizes. The mass is then poured into water, the precipitated matter filtered and washed with much water. The brominated ketone thus obtained is debrominated by violent agitation with zinc dust in glacial acetic acid on the boiling water-bath. The mass is then filtered, washed and the solution precipitated by means of water. The precipitate is extracted with ether, the ethereal solution shaken with dilute sodium carbonate solu tion and water and evaporated. It is also possible to debrominate the brominated ketone by heating a dry solution of it in benzene with an alcoholic solution of sodium iodide. In this case the solution is subsequently washed with aqueous sodium sulflte solution and water and evaporated.

From the crude product made by one or the other of these methods may be obtained, for instance by recrystallizlng it from hexane or by sublimation in a high vacuum or by both methcarbazone, the A androstene-trans-ol- (17) one-(3)-benzoate of melting point 193-194 C. By saponiflcation with alcoholic potash this benzoate may be converted into the free oxyketone, namely A" -androstene-trans-ol-(1'1)- one-(3) of the formula ample can be used for oxidizing the androstenediol-l'I-benzoate.

Example 5 Into 1 liter of ethyl alcohol which has been preheated to 30 0. there are introduced first 5 grams of A -androstene-3:17-diol-3-acetate- 17-benzoate of the formula CH; CH; H

of melting point 178-180 C. and then one molecular proportion of an ethyl alcoholic potash solution containing 0.64 gram or potassium hydroxide) and the whole is thoroughly stirred for 4 hours at the aforesaid temperature. The solution is neutralized (the quantity of alkali consumed amounting to about 10 per cent.) and then highly concentrated in a vacuum and the crude product is shaken with water and ether, the ethereal solution is separated and evaporated. By crystallizing the residue from isopropyl ether A- -androstene-B zl'l-diol-l'l-benzoate is obtained in the form oi brilliant needles oi. melting point 222-223 C.

This mono-ester is oxidized with chromic acid, after bromination in glacial acetic acid, in a manner analogous to that described in Example 2. For debrominating the brominated ketone thus obtained the ketone is dissolved in benzene, the solution is carefully dried and then boiled for 3 hours in a reflux apparatus together with a solution of sodium iodide in absolute alcohol. The reaction mixture is poured into a sodium sulflte solution of 2 per cent. strength, the benzene layer which separates is removed, shaken further with a sodium sulfite solution and with I 0.00-ClHl a bicarbonate solution and then evaporated. It

ods, or by means of the sparingly soluble semiis also possible to debrominate the brominated ketone, for example, by the action of zinc in glacial acetic acid or in a mixture of benzene and alcohol. In these cases the reaction mixture is filtered, the filtrate is mixed with water and ether and after separation into layers the upper layer is washed with a dilute sodium carbonate solution and with water and then evaporated. The crude A -androstene-3-one-17-ol-benzoate of the formula CH CH1 H Example 6 2.1 grams of androstane-diol-(3z1'7) o! the formula the I'I-mono-aceta'te of androstane-diol-(3z17) which melts at 192 C. This ester is oxidized in the manner described in Example 1, and it required the oxidation product is saponified to yield androstane-ol-(1'7) -one-(3) oi the formula CH3 OH;

i i k/ of melting point 182 C.

Example 7 2.9 grams A -androstene-diol-(Iizl'l) oi the formula CH: CH:

of melting point 182-183 C. and 0.8 gram of acetyl chloride are brought to reaction in pyridine. The reaction mixture is poured into water, the pyridine is neutralized by addition of an acid, the precipitated crude product is extracted with ether and the ethereal solution is washed and evaporated. Fractional crystallization of the residue from hexane yields pure A -1'l-acetoxy-- androstene-ol-(ii) of melting point 146-148 C.

The mono-ester so obtained is brominated, oxidized with chromic acid in glacial acetic acid and debrominated with zinc dust and acetic acid in the manner described in Example 2, whereby there is obtained in the keto-ester, namely A androstene-ol- (17) -one-(3) -acetate 01 melting point 141 C., which it required can be converted by saponiflcation into the A -androstene-ol- (17) -one-(3) of the formula of melting point 155 C.

In an analogous manner by partial benzoylation instead of acetylation A -andr ostene-diol- (3:17) can be converted by way of its i'l-monobenzoate of melting point 222-223 C. into the A androstene-ol-(l'l)-one-(3)-benzoate of melting point 194-195 C.; it required the latter can be converted by saponiflcation into the above described A -androstene-ol- (17) -one- (3) of melting point 155 C.

' Example 8 2 grams of A "-androstene-3zl'l-diol-l'l-benzoate of the formula of melting point 222-223 C.. obtainable as an intermediate product in the processes of Examples 4, 5 and '7, and 2 grams of copper powder are heated at 225 C. in a vacuum until evolution of gas has ceased. The mass is then treated with 20 cc. of alcohol, the solution filtered, the solid matter washed and the filtrate is poured into 200 cc. of water and extracted with ether. The ethereal solution is washed with sodium carbonate solution and water and evaporated. From the residuethe A -androstene-ol- (17) -one- (3) benzoate of melting point 193-194" C. is isolated,

. for example by re-crystallization irom isopropyl ether and/or sublimation in a high vacuum or by conversion into its sparingly soluble semicarbazone. By saponiflcation with alcoholic alkali f solution the benzoate is converted into the free oxy-ketone, namely A -androstene-ol- (1'7-one- (3) oi! the formula of melting point C.

Instead of starting from the l'l-monobenzoate the A='-androstene-3:l7-diol may be used and converted directly into the free A '-androsteneo1-(l7)-0ne-(3).

Instead of copper another metal catalyst sue as palladium, platinum, silver or the like can be 'used for the dehydrogenation.

Example 9 2 grams of androstane-Sfl'l-diol-i'l-acetate or the formula The etheral solution is washedkwith .water,

dried and evaporated in a vacuumi The residue is saponified while warm with alcoholic alkali solution of 2 per cent. strength and the saponiilcation mixture is poured into water and the whole extracted with ether. The ethereal solution is washed repeatedly with sodium carbonate solution and then with water, whereafter it is evaporated in a vacuum. From the residue androstane-o1-(17)-one-(3) of the formula em CH:

of melting point 182 C. is obtained, for example by recrystallization and/or sublimation in a high vacuum, or by conversion into a sparingly soluble derivative, such as the semicarbazone or dinitrov phenylhydrazone derivative.

Instead of a mixture of androstane-diol-l'lacetate and cinnamic acid there may be used an androstane-Szl'I-diol-l'l-cinnamic acid ester, in which the hydroxyl group to be dehydrogenated and the hydrogen acceptor are united in the same molecule.

Example 10 3.06 grams of l'l-methyi-androstane-diol-.

H of melting point 18s c. are dissolved in 50 cc. of glacial acetic acid and, at room temperature,

. there is added in drops a solution of 0.8 gram of chromium trioxide'in 50 cc. of glacial acetic acid.

. asoasso The chromic acid is somewhat rapidly consumed; the whole is allowed to stand for 3 hours at room temperature, then poured into water and the product thus precipitated is dissolved in ether. The ethereal solution is washed with dilute caustic soda solution and water and dried over anhydrous sodium sulfate. From the strongly concentrated ethereal solution the l'l-methyl-androstane-ol-(l'l) -one-(3) of the formula crystallizes. By recrystallization from dilute'alcohol it is purified and then melts at 192 C. The semicarbazone obtained in the usual manner melts, after recrystallization from absolute alcohol, at 235 C. while decomposing.

In a similar manner from 17-ethyl-androstane-diol-(lizl'l) of melting point 205' C. there is obtained the l'l-ethyl-androstane-ol-(l'l)-one- (3) of melting point l26-127 C. and from 3- transor 3-cis-l'letrans-androstane-diols the androstane-ol-(l'D-one- (3) of melting point 182 C.

The reaction proceeds in analogous manner with compounds containing in the 1'1 position a substituted hydroxyl group, such as an acyloxyor an alkoxy-group.

Example 11 3.04 grams of A -1'l-metl'iyl-androstene-diol- (3:17) of the formula of melting point 202-204 C. are dissolved in 50 cc. of glacial acetic acid and mixed with a solution of 1.6 grams of bromine in 10 cc. of glacial acetic acid. To this solution there is added, by drops, one of 0.8 gram of chromium trioxide in 50 cc. of glacialacetic acid. After several hours standing at room temperature the whole is poured into water, the precipitated dibromide is filtered, washed and treated in glacial acetic acid solution with 3 grams of zinc dust. The filtered solution'is then poured into water and the precipitated A -1'l-methyl-androstene ol (17) one- (3) of the formula H: CH; Cm

Id e].

ample may be used as solvent for the debromination.

In a similar manner A -androstene-ol- (17)- one-(3) of melting point 155 C. can be obtained from A =-androstene-diol-(3:17) of melting point l82-183 C.

One may also start from compounds which are acylated in l'l-position or substituted in another manner.

Example 12 2.88 grams of androstane-dione-(3:17) of the formula C H: CH;

of melting point 134 C. are dissolved in 30 cc. of methyl alcohol and into this solution there is gradually introduced, at boiling temperature, the calculated quantity of sodium. When reduction is complete a precipitate is produced by pouring the mass into water; this is then filtered, washed with much water and dried over phosphorus may be separated from it with the aid of digitonin or by way of the semicarbazone and recrystallized from hexane or dilute alcohol for purification.

Example 13 2.86 grams of A -androstene-dione-(3:17) of the formula CHa' Am .91 i

of melting point 173-174 C. are dissolved in alcohol and hydrogenated with the aid of a nickel catalyst. culated for one molecule has been absorbed, hydrogenation is interrupted, the catalyst is filtered from the solution, and the latter is poured into 400 cc. of water. The mass is extracted with When the amount of hydrogen calether and the ethereal solution is washed with water and evaporated in a vacuum. The residue is esterified by heating for a short time with a few cc. of acetic anhydride; the latter is then evaporated and the residue fractionally crystallized from dilute acetone. In this manner one obtains the A -androstene-ol-(1'l)-one-(3)- acetate of melting point 141.C. By saponification the corresponding free oxy-ketone is produced, namely A -ai'iclrostei'ie-o1-(l'll-one- (3) of the formula CH; CH; n

l of melting point C.

What we claim is:

1. A process for the manufacture of a compound of the 10,13-dimethylcyclopentanopolyhydrophenanthrene series, comprising oxidizing the 3-carbinol group of a 10,13-dimethylcyclopentanopolyhydrophenanthrene-3:ll-diol to a keto group.

2. A process for the manufacture of a compound of the cyclopentanopolyhydro-10,13-dimethylphenanthrene series, comprising oxidizing the 3-carbinol group of a 10,13-dimethylcyclopentanopolyhydrophenanthrene-3:1'7-diol to a ketone group by means of a dehydrogenating a ent.

3. A process as claimed in claim 2, wherein copper is used as a dehydrogenating agent. 4. A process for the manufacture or a compound of the cyclopentanopolyhydrophenanthrene series, comprising oxidizing the 3-carbinol group of a, compound of the formula CH3 CH fl- N d 11:

wherein R stands for a monovalent hydrocarbon radical, to a keto group.

' 5. A process for .the manufacture of a compound of the cyclopentanopolyhydrophenanthrene series, comprising oxidizing the 3-carbinol group of a compound of the formula CH; CH;

threne series, comprising oxidizing the 3-carbinol group of a compound of the formula CH: CH;

l l Hobs;

wherein R stands for a monovalent hydrocarbon radical, to a keto group.

7 A process for the manufacture of a compound of the cyclopentanopolyhydrophenanthrone series, comprising oxidizing the 3-carbinol group or a compound oi. the formula CH; CH; RY

PH /Y\/ i wherein R stands for a monovalent hydrocarbon radical, to a keto group with temporary, protection of the carbon double bond present, the temporary protection being efiected by the addition 01 hydrogen halide before oxidation, and removal of the hydrogen halide by hydrogen halide eliminating agents after oxidation.

10. A process for the manufacture of a compound of the cyclopentanopolyhydrophenanthrene series, comprising oxidizing the 3-carbinol group of a compound of the formula I H Refill to a keto group with temporary protection of the carbon double bond present, the temporary protection being eil'ected by the addition 01' hydrogen halide before oxidation, and removal of the hydrogen halide by hydrogen halide eliminating agents after oxidation. I

11. A process as claimed in claim 10, wherein copper oxide is used as the oxidizing agent.

12. The saturated 3-keto-10,13-dimethyl cyclopentanopolyhydrophenan-threnes containing in the 17-position the group I wherein R1 stands for a monovalent hydrocarbon radical and R: is a member of the group consisting of a free, an esteriiied and an etherifled hydro rl.

13. The compounds oi the formula p wherein R1 stands for a monovalent hydrocarbon radical, and Rs is a member or the group consisting of a free, an esterifledand an'etherified hydroxyl.

14; The compounds of the formula CH: OH: R

t? wherein R stands for a monovalent hydrocarbon radical.

15. The compound of the formula on. cm'

forming colorless crystals of melting point 192 C.

16. The compound of the formula cm on,

e ilggmigg colorless crystals of melting point 126- 1'2. The compounds or the formula Cm 0H.

wherein R1 stands for a monovalent hydrocarbon radical, and Re is a member of the group consisting of a free, an esterifled and an etherifled hydroxyl,

18. The compounds of the formula wherein R stands for a radical.

monovalent hydrocarbon 19. The compound of the formula CH1 CH; CH

forming colorless crystals of melting point 163 164 C.

20. A method for the production of 17-hydroxy-3-keto compounds of the cyclopentanopolyhydrophenanthrene series, which comprises subjecting a compound of the cyclopentanopolyhydrophenanthrene series of the general formula C19HnR1R2X, wherein n stands for an even number from 26 to 28, inclusive, and R1 represents a free secondary alcoholic group at the carbon atom 3, wherein R2 is at the l7-position and stands for a member'of the group consisting of a hydroxyl group and a group that can be transformed into a secondary alcoholic group with the aid of hydrolysis, while X is likewise at the 17- position and indicates a hydrocarbon radical, to the action of an oxidizing agent capable of transforming a secondary alcoholic group into a keto group.

LEOPOLD RUZICKA.

ALBERT WE'I'I'STEIN. 

